Flavone Glycosides Research Articles

Component analysis of Cucumis melo L. leaves and their antioxidant activity

Cucumis melo var. reticulatus Ser. (or netted melon ‘Earl’s Favourite’), a variety of Cucumis melo L., is widely cultivated in Shizuoka, Japan. However, the leaves and stems are discarded after harvest. Therefore, we investigated the chemical constituents of melon leaves to suggest potential applications. Air-dried melon leaves were extracted using methanol. The methanol extract was suspended in water and successively partitioned using n-hexane, ethyl acetate, and to yield each fraction. Eight flavone glycosides (1 − 8) and three terpenes (9 − 11) were obtained. The chemical structures of these compounds were determined via nuclear magnetic resonance and mass spectrometry. The antioxidant activity of compounds 1 − 8 was evaluated using a 2,2-diphenyl-1-picrylhydrazyl radical assay. All compounds showed radical-scavenging activity in the range of IC50, 24.2 − 129.5 μM, which depended on the number of hydroxyl groups on the benzene ring and ortho-substitution. Therefore, the leaves of C. melo may be considered valuable material for developing antioxidants.

Rutin loaded bilosomes for enhancing the oral activity and nephroprotective effects of rutin in potassium dichromate induced acute nephrotoxicity in rats

Rutin, a flavone glycoside, has shown to have a significant beneficial kidney protection effect in drug-induced nephropathy. However, its poor solubility and low oral bioavailability have limited its pharmacological applications. This study aimed at formulating rutin-loaded bilosomes to enhance the renal protective effect of rutin for oral application. Rutin-loaded bilosomes were developed using thin-film hydration technique. The prepared formulations were characterized by entrapment efficiency percentage (EE%), vesicular size (VS) and zeta potential (ZP) measurement. The developed formula exhibited moderate EE%, ranging from 20.02 ± 2.85 to 48.57 ± 3.57%, suitable VS results that ranged from 502.1 ± 36 to 665.1 ± 45 nm and high ZP values (≤ -41.4 ± 7.27 mV). Transmission electron microscopy revealed the spherical shape of the developed bilosomes. The in-vitro release study revealed prolonged release of rutin from bilosomes, relative to free drug. F2, prepared using the molar ratio span 60: cholesterol: sodium cholate 1:1:0.5, was selected for further investigations as it showed the highest EE%, smallest VS, optimum ZP, and persistent release profile. In-vivo studies were performed on drug-induced nephropathy in rats. Acute renal failure was induced using a single dose of potassium dichromate (PDC; 15 mg/kg; i.p). The selected formulation, F2, alleviated kidney dysfunction, oxidative stress and inflammation via decreasing MDA, TNF-α and TGF-β and increasing GSH. In addition, F2 promoted Akt/PI3K activation against PDC-induced acute renal failure. Histopathology results came in accordance with in-vivo results. Thus, bilosomes could be considered a potential delivery system for enhancing the oral delivery and kidney protection activity of rutin.

A New Isoflavone Xylopyranoside and Isoflavone Derivatives from the Roots of Ochna integerrima and Their DPPH Radical Scavenging Activity.

O chna integerrima (Louri) Merr. is one of the two species of the genus Ochna (family Ochnaceae) found in Thailand. Its bark is used in traditional Thai medicine to treat digestive disorders. Phytochemical investigation of the crude MeOH extract of the root woods of O. integerrima furnished an unreported isoflavone glycoside, gerontoisoflavone A-4'-O-β-D-xylopyranoside (1), together with the previously described irisolone methyl ether (2), iriskumaonin methyl ether (3), iriskumaonin (4), gerontoisoflavone A (5), isoprunetin (6), a flavone glycoside, vitexin (7), and a chromone derivative, lophilone A (8). The structure of 1 was elucidated by 1D and 2D NMR spectral analysis as well as HRMS data. Compounds 1-7 were evaluated for their 2,2-diphenyl-1-picrylhydrazil radical(DPPH●) scavenging activity and antiplasmodial activity against a chloroquine- and pyrimethamine-resistant strain of Plasmodium falciparum (K1). Compounds 5 exhibited strongest scavenging activity, with a scavenging concentration at 50% (SC50) of 137.7 mM, while 4 and 6 displayed weak scavenging activity, with SC50 values of 4 and 5 times higher than that of 5. None of the tested compounds showed antiplasmodial activity against P. falciparum (K1) at a concentration of 5 mg/mL.

Metabolomics and chemometrics-driven valorisation of mango leaves: Unveiling putative α-amylase and α-glycosidase inhibitory metabolites

This study presents a comprehensive investigation into the metabolite composition of various mango leaf samples using Ultra Performance Liquid Chromatography-High Resolution Mass Spectrometry (UPLC-HRMS). A total of 103 chromatographic peaks representing diverse metabolite groups were annotated, revealing significant variations in chemical composition among different mango varieties. Polyphenols emerged as the most abundant class, with mangiferin being the major polyphenol detected in most varieties, including Awis, Sukari, Sinara, Sedika, and Alfonse. Trihydroxybenzoyl mangiferin was predominant in Sedika and Alfonse varieties. Flavonoids, such as flavanone glycosides and flavone glycosides, were also prominent. O-methylnaringenin pentoside was the major flavanone glycoside detected in Awis, Sukari, and Sinara varieties, while naringenin-O-hexoside was predominant in Alfonse. Phenolic acids were detected across all varieties, with protocatechuic acid and gallic acid being major components. Protocatechuic acid was identified in all varieties except Sedika and Naomi, where gallic acid dominated. Kaempferol and di-O-methylquercetin were exclusively detected in the Naomi variety. In-vitro enzyme inhibition assays against α-amylase and α-glycosidase enzymes revealed dose-dependent inhibitory effects of mango leaf extracts, with variations in potency among varieties. The most potent inhibitors of α-amylase activity were found in extracts from Sukari and Alfonse leaves, while those from Sukari and Sedika leaves showed the strongest inhibition of α-glycosidase activity. Interestingly, the extracts that exerted the highest inhibition of α-amylase activity did not necessarily inhibit α-glycosidase activity significantly. Additionally, glucose uptake promotion assays identified Awis and Sedika leaves as the most potent promoters of glucose uptake.

Profiling of Phytochemicals in the Leaves of Asystasia gangetica (L) T. Anderson using GC-MS and HPLC Analysis

Asystasia gangetica is a perennial herb that has naturalized in Africa and Asia, where it is use in treatment of varying ailments such as lowering of blood sugar, sexually transmitted infections, reduce swelling and ear disease. The presence of phytochemicals in this plant may be responsible for its acclaimed effects. This study aims to identify the phytoconstituents in the leaves of Asystasia gangetica. Preliminary phytochemical screening was achieved by standard methods, GC-MS and HPLC analyses were utilized to determine volatile and non-volatile compounds. Phytochemicals identified include alkaloids, tannins, steroids, saponins, flavonoids, and glycosides. GC-MS analysis identified twenty-eight compounds with Z-(13,14-Epoxy)tetradec-11-en-1-olacetate (8.72 %); Octadecane, 1-(ethenyloxy)- (8.77 %); Cycloheptano[d]imidazolidine, 1,3- (9.81 %); cis-Vaccenic acid (10.20 %); 15-Hydroxypentadecanoic acid (11.94 %) as the prominent compounds and HPLC evaluation reported the most prominent compounds such as proanthocyanidin (6.69 %), flavone (7.51 %), spartein (7.64 %), aphylidine (10.33 %) and cyanogenic glycoside (10.51 %) respectively. Identification of these compounds with documented evidence of pharmacological activities, thus validate the use of Asystasia gangetica, in many disease conditions.

A review of phytopharmacology and formulation of sphaeranthus indicus

Sphaeranthus indicus Linn., belonging to the Asteraceae family, It thrives abundantly in damp areas, including as a weed in rice fields across India. In traditional Indian medicine, many different components of the plant, including the leaves, cortex, wood, roots, flower, and seed, are used to cure a variety of illnesses. Astringent, stomachic, refreshing, and externally calming are some of the qualities associated with the herb. Sphaeranthus indicus is rich in diverse secondary metabolites, including eudesmanolides, sesquiterpenoids, sesquiterpene lactones, sesquiterpene acids, flavone glycosides, flavonoid C-glycosides, is flavone glycoside, sterols, sterol glycosides, alkaloids, peptide alkaloids, amino acids, and sugars. Essential oils extracted from its flowers and whole plants contain monoterpene hydrocarbons, oxygenated monoterpenes, sesquiterpene hydrocarbons, and oxygenated sesquiterpenes. This comprehensive review encompasses the structure, botanical compounds composition, ethnobotanical uses, and pharmacological activities reported for Sphaeranthus indicus. It underscores the vast medicinal potential of this plant and highlights its importance in traditional and modern medicinal practices.

Simultaneous High-Performance Recovery and Extended Acid-Catalyzed Hydrolysis of Oleuropein and Flavonoid Glycosides of Olive (Olea europaea) Leaves: Hydrothermal versus Ethanol Organosolv Treatment.

Olive leaves (OLLs) are an exceptional bioresource of natural polyphenols with proven antioxidant activity, yet the applicability of OLL extracts is constrained by the relatively high polarity of the major polyphenols, which occur as glycosides. To overcome this limitation, OLLs were subjected to both hydrothermal and ethanol organosolv treatments, fostered by acid catalysis to solicit in parallel increased polyphenol recovery and polyphenol modification into simpler, lower-polarity substances. After an initial screening of natural organic acids, oxalic acid (OxAc) was found to be the highest-performing catalyst. The extraction behavior using OxAc-catalyzed hydrothermal and ethanol organosolv treatments was appraised using kinetics, while treatment optimization was accomplished by deploying response-surface methodology. The comparative assessment of the composition extracts produced under optimal conditions of residence time and temperature was performed with liquid chromatography-tandem mass spectrometry and revealed that OLLs treated with 50% ethanol/1.5% HCl suffered extensive oleuropein and flavone glycoside hydrolysis, affording almost 23.4 mg hydroxytyrosol and 2 mg luteolin per g dry weight. On the other hand, hydrothermal treatment with 5% OxAc provided 20.2 and 0.12 mg of hydroxytyrosol and luteolin, respectively. Apigenin was in all cases a minor extract constituent. The study presented herein demonstrated for the first time the usefulness of using a natural, food-grade organic acid to perform such a task, yet further investigation is needed to maximize the desired effect.

Rapid identification of chemical components and screening of acetylcholinesterase inhibitors from Dalbergia odorifera based on mass defect and diagnostic ion filtering strategy, affinity ultrafiltration, and liquid chromatography-tandem mass spectrometry.

Dalbergia odorifera is a natural product rich in pharmacological ingredients, but the comprehensive characterization and rapid profiling of active components remain a challenge. Thus, an integrated data mining and identification strategy was exploited to efficiently identify the chemical constituents and screen acetylcholinesterase inhibitors (AChEIs) through affinity ultrafiltration and ultra-high-performance liquid chromatography-mass spectrometry (AUF-UHPLC-MS). As a result, polygonal mass defect filtering, diagnostic product ions, and neutral loss rules were created for rapid structural classification and component identification. A total of 140 flavonoids were tentatively characterized, including 41 isoflavonoids, 23 flavanones, 21 isoflavans, 19 flavones and flavonols, 13 neoflavonoids, 11 isoflavanones, seven flavone glycosides, and five chalcones. Subsequently, six natural AChEIs including tectorigenin, fisetin, dalbergin, pterostilbene, isoliquiritigenin, and biochanin A were screened out using AUF-UHPLC-MS and molecular docking. Meanwhile, the AChE inhibitory activities of the six compounds were assessed in vitro, tectorigenin, fisetinand, and dalbergin have moderate inhibitory activity. In conclusion, a novel strategy for systematic characterization and further screening of active compounds in natural products was established, which provides a material basis for quality control of Dalbergia odorifera.

Determination of eleven components in rat plasma by UPLC-MS/MS and GC-MS for pharmacokinetic studies after oral administration of Citri Reticulatae Pericarpium extract

Citri Reticulatae Pericarpium (CRP) is used as common health-care food and traditional Chinese medicine (TCM), which exerts pharmacological effects, such as anti-cardiovascular, anti-tumor, anti-oxidant, anti-inflammatory, anti-virus, hepatoprotective, blood pressure-lowering and neuroprotective. In this study, reliable, and sensitive ultra-high performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) and gas chromatography-mass spectrometry (GC-MS) methods were developed and validated for the determination of eleven active components in rat plasma after oral administration of the CRP extract. The results of this method exhibited that the specificity, linearity (r > 0.999), precision and accuracy (the coefficient of variation (CV) < 11.5 %), recovery (52.9–107.9 %), matrix effects (63.8–107.5 %), and stability (CV < 10.8 %) met all requirements for the quantitation of plasma samples. The pharmacokinetic results showed that the Tmax of flavone glycosides was less than 0.7 h, and that of polymethoxyflavones and volatile components were within 1–7 h. Meanwhile, the area-under-the-curve (AUC) and concentration maximum (Cmax) of hesperidin, nobiletin, tangeretin, and D-limonene were higher than those of the other components, suggesting that the plasma exposure levels of these constituents were higher in CRP. The present research lays a foundation for elucidating the therapeutic material basis and provides a reference for further scientific research and clinical application of CRP.

Uncovering Metabolic Alterations in HCT-116 Colon Cancer Cells upon Exposure to Bamboo Leaf Extract Obtained from Guadua incana Londoño.

Metabolic alterations are increasingly recognized as important aspects of colorectal cancer (CRC), offering potential avenues for identifying therapeutic targets. Previous studies have demonstrated the cytotoxic potential of bamboo leaf extract obtained from Guadua incana (BLEGI) against HCT-116 colon cancer cells. However, the altered metabolic pathways in these tumor cells remain unknown. Therefore, this study aimed to employ an untargeted metabolomic approach to reveal the metabolic alterations of the endometabolome and exometabolome of HCT-116 cells upon exposure to BLEGI treatment. First, a chemical characterization of the BLEGI was conducted through liquid chromatography coupled with mass spectrometry (LC-MS). Next, we assessed cell viability via MTT and morphological analysis using an immunofluorescence assay against colon cancer cells, and anti-inflammatory activity using an LPS-stimulated macrophage model. Subsequently, we employed LC-MS and proton nuclear magnetic resonance (1H-NMR) to investigate intra- and extracellular changes. Chemical characterization primarily revealed the presence of compounds with a flavone glycoside scaffold. Immunofluorescence analysis showed condensed chromatin and subsequent formation of apoptotic bodies, suggesting cell death by apoptosis. The results of the metabolomic analysis showed 98 differential metabolites, involved in glutathione, tricarboxylic acid cycle, and lipoic acid metabolism, among others. Additionally, BLEGI demonstrated significant nitric oxide (NO) inhibitory capacity in macrophage cells. This study enhances our understanding of BLEGI's possible mechanism of action and provides fresh insights into therapeutic targets for treating this disease.

A new iridoid glycoside and other secondary metabolites from Sideritis dichotoma Huter and their chemotaxonomic significance

The phytochemical studies on the aerial parts of Sideritis dichotoma led to the isolation and identification of a new iridoid glycoside (1), along with four known iridoid glycosides (2-5), three phenylethanoid glycosides (6–8), two flavone glycosides (9 and 10), one neolignan (11) and a megastigmane glycoside (12). Their structures were elucidated by spectroscopic techniques. Compounds 2, 3 and 12 have never been found in the Sideritis genus before. Furthermore, eleven compounds (1–5, 7–12) were characterized for the first time from S. dichotoma. The chemotaxonomic importance of isolated compounds was discussed. This is the first phytochemical study on the polar constituents of S. dichotoma, an endemic species to Türkiye.

Implications of the Propagation Method for the Phytochemistry of Nepeta cataria L. throughout a Growing Season.

Catnip (Nepeta cataria L.) plants produce a wide array of specialized metabolites with multiple applications for human health. The productivity of such metabolites, including nepetalactones, and natural insect repellents is influenced by the conditions under which the plants are cultivated. In this study, we assessed how field-grown catnip plants, transplanted after being propagated via either single-node stem cuttings or seeds, varied regarding their phytochemical composition throughout a growing season in two distinct environmental conditions (Pittstown and Upper Deerfield) in the state of New Jersey, United States. Iridoid terpenes were quantified in plant tissues via ultra-high-performance liquid chromatography with triple quadrupole mass spectrometry (UHPLC-QqQ-MS), and phenolic compounds (phenolic acids and flavonoids) were analyzed via UHPLC with diode-array detection (UHPLC-DAD). The highest contents of total nepetalactones in Pittstown were found at 6 weeks after transplanting (WAT) for both seedlings and cuttings (1305.4 and 1223.3 mg/100 g, respectively), while in Upper Deerfield, the highest contents for both propagules were at 11 WAT (1247.7 and 997.1 mg/100 g, respectively) for seed-propagated and stem cuttings). The highest concentration of nepetalactones was associated with floral-bud to partial-flowering stages. Because plants in Pittstown accumulated considerably more biomass than plants grown in Upper Deerfield, the difference in nepetalactone production per plant was striking, with peak productivity reaching only 598.9 mg per plant in Upper Deerfield and 1833.1 mg per plant in Pittstown. Phenolic acids accumulated in higher contents towards the end of the season in both locations, after a period of low precipitation, and flavone glycosides had similar accumulation patterns to nepetalactones. In both locations, rooted stem cuttings reached their maximum nepetalactone productivity, on average, four weeks later than seed-propagated plants, suggesting that seedlings have, overall, better agronomic performance.

The potential of baicalin to enhance neuroprotection and mitochondrial function in a human neuronal cell model

Baicalin is a flavone glycoside derived from flowering plants belonging to the Scutellaria genus. Previous studies have reported baicalin’s anti-inflammatory and neuroprotective properties in rodent models, indicating the potential of baicalin in neuropsychiatric disorders where alterations in numerous processes are observed. However, the extent of baicalin’s therapeutic effects remains undetermined in a human cell model, more specifically, neuronal cells to mimic the brain environment in vitro. As a proof of concept, we treated C8-B4 cells (murine cell model) with three different doses of baicalin (0.1, 1 and 5 μM) and vehicle control (DMSO) for 24 h after liposaccharide-induced inflammation and measured the levels of TNF-α in the medium by ELISA. NT2-N cells (human neuronal-like cell model) underwent identical baicalin treatment, followed by RNA extraction, genome-wide mRNA expression profiles and gene set enrichment analysis (GSEA). We also performed neurite outgrowth assays and mitochondrial flux bioanalysis (Seahorse) in NT2-N cells. We found that in C8-B4 cells, baicalin at ≥ 1 μM exhibited anti-inflammatory effects, lowering TNF-α levels in the cell culture media. In NT2-N cells, baicalin positively affected neurite outgrowth and transcriptionally up-regulated genes in the tricarboxylic acid cycle and the glycolysis pathway. Similarly, Seahorse analysis showed increased oxygen consumption rate in baicalin-treated NT2-N cells, an indicator of enhanced mitochondrial function. Together, our findings have confirmed the neuroprotective and mitochondria enhancing effects of baicalin in human-neuronal like cells. Given the increased prominence of mitochondrial mechanisms in diverse neuropsychiatric disorders and the paucity of mitochondrial therapeutics, this suggests the potential therapeutic application of baicalin in human neuropsychiatric disorders where these processes are altered.

Inhibitory Efficacy of Main Components of Scutellaria baicalensis on the Interaction between Spike Protein of SARS-CoV-2 and Human Angiotensin-Converting Enzyme II.

Blocking the interaction between the SARS-CoV-2 spike protein and the human angiotensin-converting enzyme II (hACE2) protein serves as a therapeutic strategy for treating COVID-19. Traditional Chinese medicine (TCM) treatments containing bioactive products could alleviate the symptoms of severe COVID-19. However, the emergence of SARS-CoV-2 variants has complicated the process of developing broad-spectrum drugs. As such, the aim of this study was to explore the efficacy of TCM treatments against SARS-CoV-2 variants through targeting the interaction of the viral spike protein with the hACE2 receptor. Antiviral activity was systematically evaluated using a pseudovirus system. Scutellaria baicalensis (S. baicalensis) was found to be effective against SARS-CoV-2 infection, as it mediated the interaction between the viral spike protein and the hACE2 protein. Moreover, the active molecules of S. baicalensis were identified and analyzed. Baicalein and baicalin, a flavone and a flavone glycoside found in S. baicalensis, respectively, exhibited strong inhibitory activities targeting the viral spike protein and the hACE2 protein, respectively. Under optimized conditions, virus infection was inhibited by 98% via baicalein-treated pseudovirus and baicalin-treated hACE2. In summary, we identified the potential SARS-CoV-2 inhibitors from S. baicalensis that mediate the interaction between the Omicron spike protein and the hACE2 receptor. Future studies on the therapeutic application of baicalein and baicalin against SARS-CoV-2 variants are needed.

Analogues of Dihydroflavonol and Flavone as Protein Tyrosine Phosphatase 1B Inhibitors from the Leaves of Artocarpus elasticus.

Protein tyrosine phosphatase 1B (PTP1B) is one of the target enzymes whose disruption leads to obesity and diabetes. A series of PTP1B inhibitors were isolated from the leaves of Artocarpus elasticus, used in traditional medicines for diabetes. The isolated inhibitors (1-13), including two new compounds (1 and 2), consisted of dihydroflavonols and flavones. The structural requirements for the PTP1B inhibitory mode and potency were revealed in both skeletons. The two highest PTP1B inhibitory properties were dihydroflavonol 1 and flavone 6 analogs with IC50 values of 0.17 and 0.79 μM, respectively. The stereochemistry also affected inhibitory potencies: trans isomer 1 (IC50= 0.17 μM) vs cis isomer 2 (IC50= 2.24 μM). Surprisingly, the dihydroflavonol and flavone glycosides (11 and 13) displayed potent inhibition with IC50s of 2.39 and 0.22 μM, respectively. Furthermore, competitive inhibitor 1 was applied to time-dependence experiments as a simple slow-binding inhibitor with parameters of Kiapp = 0.064103 μM, k3 = 0.2262 μM-1 min-1, and k4 = 0.0145 min-1. The binding affinities by using the fluorescence quenching experiment were highly correlated with inhibitory potencies: 1 (IC50= 0.17 μM, KSV = 0.4375 × 105 L·mol-1) vs 3 (IC50= 17.79 μM, KSV = 0.0006 × 105 L·mol-1). The specific binding interactions were estimated at active and allosteric sites according to the inhibitory mode by molecular docking.

Antimicrobial and Phytochemistry in Lichens

Abstract: The present study conducted with the antimicrobial and phytochemical properties in Lichen. Lichen product have been used in traditional medicine for accent period. Indian populated Lichen species like, Parmotrema perlatum, Cetraria Islandica, Bryoria fremontil was most widely used liken were chosen for the study. The extract present with Flavonic Glycosides, Saponins, Volatil Oil, Cummarins, Qunine and Carotenoids. The antimicrobial activity come out by agar well diffusion method. The ethyl acetate fraction of Bryoria fremontil and Cetraria Islandica was found to most effective against all bacterial pathogen and fungus phytopathogens. The extract of Cetraria and parmotrema found to be most inhibiting fungal pathogens as compared to bacterial. The Lichen extract tested antimicrobial activity which suggest their use in treatment of various disease caused by microorganism

Cosmosiin Induces Apoptosis in Colorectal Cancer by Inhibiting PD-L1 Expression and Inducing ROS.

Immunotherapies, particularly those concerning immune checkpoint inhibitors, have transformed cancer treatment in recent years. Programmed death-ligand 1 (PD-L1) is a key target for immunotherapy that is overexpressed in the cells of colorectal cancer, a widespread malignant cancer that poses a significant healthcare challenge. This study investigated the effects of cosmosiin treatment on colorectal cancer cell lines. Cosmosiin is a naturally occurring flavone glycoside compound that has potential health benefits, including antioxidant and immunomodulatory effects. This study showed that cosmosiin effectively suppresses the expression of PD-L1 and triggers apoptosis, which is facilitated through pathways that are related to reactive oxygen species. These outcomes suggest that cosmosiin could be a promising candidate for an immune checkpoint inhibitor in the treatment of colorectal cancer.

Diosmin ameliorates LPS-induced depression-like behaviors in mice: Inhibition of inflammation and oxidative stress in the prefrontal cortex

Diosmin is a flavone glycoside with a confirmed therapeutic effectiveness on the chronic venous disorders. In this paper, the classical mouse depression model induced by LPS was established to explore the effect of Diosmin on depression. Firstly, we found that Diosmin could inhibit the inflammation and neuronal damage in the prefrontal cortex (PFC) of mice, and thus alleviating the LPS-induced depressive-like behaviors. Specifically, Diosmin treatment significantly suppressed the secretion of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β), reduced the activation of microglia, and inhibited the expression of NLRP3 inflammasome and its downstream effector caspase-1 in both PFC of mice and BV2 microglial cells exposed to LPS. Then, we demonstrated that pretreatment with Diosmin dramatically suppressed the LPS-induced oxidative stress in the PFC of mice, manifested in the decrease of reactive oxygen species and malondialdehyde while increase of catalase activity. Consistently, Diosmin also alleviated the oxidative stress in BV2 cells exposed to LPS. Finally, we confirmed that Diosmin effectively suppressed the activation of NF-κB signaling pathway in the PFC of LPS-treated mice. Further in vitro experiments also verified that Diosmin could prevent the p65 transposition to nucleus in LPS-treated BV2 cells, suggesting that the antidepressant effects of Diosmin are partially mediated by blocking of NF-κB signaling. Taken together, this study proposes the potential antidepressant effect of Diosmin, which provides useful support to the development of new therapies for depression.

Properties of Dietary Flavone Glycosides, Aglycones, and Metabolites on the Catalysis of Human Endoplasmic Reticulum Uridine Diphosphate Glucuronosyltransferase 2B7 (UGT2B7)

Flavone glycosides, their aglycones, and metabolites are the major phytochemicals in dietary intake. However, there are still many unknowns about the cellular utilization and active sites of these natural products. Uridine diphosphate glucuronosyltransferases (UGTs) in the endoplasmic reticulum have gene polymorphism distribution in the population and widely mediate the absorption and metabolism of endogenous and exogenous compounds by catalyzing the covalent addition of glucuronic acid and various lipophilic chemicals. Firstly, we found that rutin, a typical flavone O-glycoside, has a stronger UGT2B7 binding effect than its metabolites. After testing a larger number of flavonoids with different aglycones, their aglycones, and metabolites, we demonstrated that typical dietary flavone O-glycosides generally have high binding affinities towards UGT2B7 protein, but the flavone C-glycosides and the phenolic acid metabolites of flavones had no significant effect on this. With the disposition of 4-methylumbelliferone examined by HPLC assay, we determined that 10 μM rutin and nicotifiorin could significantly inhibit the activity of recombinant UGT2B7 protein, which is stronger than isovitexin, vitexin, 3-hydroxyphenylacetic acid and 3,4-dihydroxyphenylacetic acid. In addition, in vitro experiments showed that in normal and doxorubicin-induced lipid composition, both flavone O-glycosides rutin and flavone C-glycosides isovitexin at 10 μM had no significant effect on the expression of UGT1A1, UGT2B4, UGT2B7, and UGT2B15 genes for 24 h exposure. The obtained results enrich the regulatory properties of dietary flavone glycosides, aglycones, and metabolites towards the catalysis of UGTs and will contribute to the establishment of a precise nutritional intervention system based on lipid bilayers and theories of nutrients on endoplasmic reticulum and mitochondria communication.

Assessment of the chemical and genetic variability among accessions of Cicerbita alpina (L.) Wallr., an alpine plant with anthelmintic properties

Cicerbita alpina(L.) Wallr, is a perennial alpine plant and a member of theAsteraceaefamily, typically found at altitudes above 1000 meters in the Italian Alps. Although previously utilized primarily as a local delicacy, recent studies have revealed strong antiparasitic activity throughin vitroexperiments. In Europe, numerous chemical drugs employed to combat nematodes — helminths that infest the digestive tract of livestock — are banned due to their environmental harm or show only reduced efficiency because of the development of resistance. Consequently, there is a growing demand for new alternative anthelmintic treatments in agricultural practices. Specialized metabolites found in the extracts ofC. alpinacould offer a sustainable and biological alternative to chemical drugs, specifically for nematode control. For this purpose, a unique germplasm collection originating from eight distinct natural populations in the Italian Alps was analyzed for its chemical diversity using state-of-the-art targeted LC-MS/MS spectrometry, including quantification based on multiple reaction monitoring. The predominant metabolites identified from the species were the caffeic acid derivatives chicoric acid, chlorogenic acid, and 3. 5-dicaffeoylquinic acid, the sesquiterpene lactone derivative 8-O-acetyl-15-ß-D-glucopyranosyl lactucin and the flavone glycosides, apigenin-7-O-glucoside and luteolin-7-O-glucoside, alongside their precursors apigenin and luteolin, respectively. Additionally, the genetic diversity of eighty individual plants within the germplasm collection was evaluated using ten DNA molecular markers (Simple Sequence Repeats), successfully transferred from two closely related species (Cichorium intybusandTanacetum parthenium). This investigation unveiled a significant range of genetic diversity within the examined populations, resulting in the establishment of three distinct genetic groups. The findings were further correlated with the original ecological environment and local climate conditions spanning a biennial period, indicating substantial variations among the different accessions and the intricate interplay between genetic background and environmental factors. These results could serve as a basis for future domestication of the species through plant breeding programs ensuring product quality, but also facilitating the cultivation ofC. alpinain more diverse geographic regions.